Introduction of whole-cell pertussis (wP) vaccines in the late 1940s resulted in a rapid reduction in both the incidence of pertussis and death caused by the infection. However, the success of these vaccines was undermined by concerns over safety issues. Thus, they were replaced with acellular pertussis (aP) vaccines in the late 1990s in many developed countries (1). Since then, pertussis cases have increased and dramatic epidemic cycles have returned. In 2012, 48,277 cases of pertussis and 18 deaths were reported to the Centers for Disease Control and Prevention (CDC), which represents the greatest burden of pertussis in the United States in 60 years and similar outbreaks are occurring in other countries (2-4). However, the epidemiology of contemporary pertussis does not replicate that of the pre-vaccine era. Disease is now more common in infants and older children (ages 9 to 19) and, strikingly, these older children are often fully vaccinated according to current recommendations yet develop pertussis (5, 6). Ominously, studies that have analyzed pertussis incidence among children that were born and vaccinated during the transition to aP vaccines have found that the rate of infection is significantly higher among children vaccinated with only aP vaccines compared to those vaccinated with even a single dose of wP vaccine (7). To combat the rise of infections in this group, regulatory agencies have called for boosters to be administered earlier (8). The benefit of boosting with aP vaccines is at best unclear because it is unknown whether the re-emergence of pertussis is due simply to waning immunity or to fundamental differences in the nature of the immune response induced by aP vaccines compared with wP vaccines or with natural infection.
The increased incidence of disease among older children and also adults is especially worrisome because of the corresponding risk of transmission to non- or incompletely-immunized infants (9). Compounding the problem, antibiotic treatment has minimal efficacy by the time most diagnoses are made and severe cases can be unresponsive to standard therapies for respiratory distress, such as mechanical ventilation (10). This re-emergence of pertussis as a global public health problem presents many challenges. For example, needed are vaccines that have an acceptable safety profile, provide long-lasting immunity, reduce infection burden and prevent transmission. Also needed are therapeutic agents and treatment strategies that reduce morbidity and mortality in vulnerable populations (11). Clearly, a strong need exists for improved pertussis vaccines.